Registration Dossier

Administrative data

Description of key information

Four studies were performed to evaluate acute oral and dermal toxicity of the test substance and a structural analogue to the rat (according or similar to OECD 401, 402). Neither the test substance nor the analogue induced any mortalities, abnormalities or clinical signs when applied oral or dermal. The LD50 for oral and dermal toxicity is considered to be > 10.000 mg/kg bw and > 2000 mg/kg bw, respectively.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
no guideline followed
Principles of method if other than guideline:
similarities to OECD guideline 401
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: CFE (RAC, SPF) strain
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: /
- Age at study initiation: /
- Weight at study initiation: 126 - 139 g
- Fasting period before study: /
- Housing: groups of 5 in macrolon cages
- Diet (e.g. ad libitum): Nafag ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 1
- Humidity (%): 55 +/- 5
- Air changes (per hr): /
- Photoperiod (hrs dark / hrs light): 14h
Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Remarks:
0.5 % in tap water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 25%
- total volume: 20 ml/kg bw

MAXIMUM DOSE VOLUME APPLIED: 10.000 mg/kg bw
Doses:
5000 and 10000 mg/kg bw
No. of animals per sex per dose:
5000 mg/kg bw : 5 per sex and dose
10000 mg7kg bw : 3 males and 2 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 8d
- Frequency of observations and weighing: /
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: no
Statistics:
no
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 10 000 mg/kg bw
Mortality:
no martalities
Clinical signs:
no clinical symptoms
Body weight:
pre-test: 131 g and 129 g
day 8: 18 3g and 184 g
Other findings:
yellow stained feces
Interpretation of results:
GHS criteria not met
Conclusions:
The acute oral LD50 was established to be > 10000 mg/kg bw.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
10 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2011
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Breeding farm VELAZ S.f.O., Kolec u Kladna, Czech Republic, RCH CZ 21760152
- Weight at study initiation: males 258 g, females 189 g
- Housing: singly
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 5d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 30 - 70
- Air changes (per hr): /
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: back
- % coverage: 10
- Type of wrap if used: semiocclusive dressing

REMOVAL OF TEST SUBSTANCE
- Washing (if done): water
- Time after start of exposure: 24h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- Concentration (if solution):
- Constant volume or concentration used: unchanged substance, constant dose level, volume individual
- For solids, paste formed: no

VEHICLE
- Amount(s) applied (volume or weight with unit):
- Concentration (if solution):
- Lot/batch no. (if required):
- Purity:
Duration of exposure:
24h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5/sex/dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: weighing before application, 8th and 15th day of study, observation daily
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs
Statistics:
not applicable
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
no
Clinical signs:
no
Body weight:
no abnormalities
Gross pathology:
no abnormalities
Interpretation of results:
GHS criteria not met
Conclusions:
According to the results of study, the value of LD50 (dermal) of the test substance is higher than 2000 mg/kg bw for rats of both sexes.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Additional information

Read across justification

Acute toxicity effects were assessed at the test item itself and, additionally, at structural analogues. All substances are calcium-salts and share high similarity in structure. Moreover, the substances are minimal soluble in water. Therefore, it is acceptable to derive additional information on acute toxicity from experimental data of the analogue substances.

Procedure and observations

To evaluate the acute oral toxicity, single doses of 5000 and 10.000 mg/kg bw of the test article were administrated to groups of male and female rats by oral gavage (Ciba 1972a). Following dosing, the animals were observed for 8d. There were no deaths as a result of treatment with the test article. Clinical signs of toxicity or changes in body weight gain were not observed during the observation period. Gross necropsy was without any findings.

In the course of a second study according OECD guideline 401, a single dose of 15.85 g/kg bw of the test item dissolved in olive oil was administrated orally to rats (Synthesia 1993). All animals survived until scheduled necropsy. Any symptoms or clinical signs did not occur. However, analytical data and purity of the test material were not confirmed by the provider. Thus, this study is regarded as not reliable.

Read across to CAS 5280 -70 -6

A structural analogue (Ba-salt) was also tested for acute oral toxicity. In a limit test similar to OECD guideline 401 a single dose of 5000 mg/kg bw of the test material dissolved in carboxymethyl-cellulose was administrated to rats by gavage (Ciba 1980). The post observation period was 14d and animals were daily checked for clinical signs and mortalities. All animals survived until scheduled necropsy, body weights were uneffected by the substance and signs of toxicity were also not observed. Pathology was without any findings.

Dermal toxicity of the test item was evaluated on a group of 6 male rats which were treated with the test article at 5000 mg/kg for 24h by dermal application (Synthesia 1993). The substance was suspended in water and administrated onto greased (ethanol:acetone 1:1) skin. Animals were examined for clinical signs and viability 0.5, 3, 12, 24 and 72h after treatment. All animals were necropsied and examined macroscopically. No deaths occurred during the study period. Neither clinical signs of systemic toxicity nor local effects of the test article on the skin at the application site were observed during the observation period. However, analytical data and purity of the test material were not confirmed by the provider. Thus, this study is regarded as not reliable.

Read across to CAS 12286-65-6

The substance was tested for acute dermal toxicity using Wistar rats. Two groups of animals (5 males and 5 females) received a single dose of 2000 mg/kg bw. The test material was applied onto shaved dorsal skin for 24 hours. The test animals were observed 14 days after exposure of the test substance, afterwards they were sacrificed, and the necropsy for macroscopic examination of the organs was performed. The test item did not cause mortalities. Clinical signs or macroscopic changes were not observed.

Discussion

Oral application of the test substance and a structural analogue did not induce any signs of toxicity. None of the animals died, viability and bodyweight gain were unaffected by the test article. Also dermal application did not induce any symptoms or mortalities. Thus, the substance is not considered to be toxic after single oral or dermal application.

Justification for classification or non-classification

Dangerous Substance Directive (67/548/EEC)

The available studies are considered reliable and suitable for classification purposes under 67/548/EEC. As a result the substance is not considered to be classified for acute toxicity under Directive 67/548/EEC, as amended for the 28th time in Directive 2001/59/EC.

 

Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance is not considered to be classified for acute toxicity under Regulation (EC) No. 1272/2008, as amended for the second time in Directive (EC 286/2011).